Abstract
Cartilage is a connective tissue that acts as a cushion between adjacent bones, providing a smooth, lubricated surface for movement. The destruction and loss of cartilage can cause osteoarthritis, a degenerative joint disease, that affects over 250 million people worldwide and is predicted to become the forth leading cause of disability by 2024. Cartilage lacks the ability to self-repair when damaged and despite recent intensive research, there is still no current regenerative treatment that provides an alternative to the existing permanent joint replacement implants. Cell-based therapies represent a promising alternative, however both chondrocytes and mesenchymal stem cell (MSCs) still fail in restoring the original structure of hyaline cartilage and will eventually form fibrocartilage which has inferior mechanical properties. The effect of stiffness on regulating MSCs differentiation and chondrocytes re-differentiation has been previously studied and appeared to affect cell behaviour by influencing cell proliferation, migration and gene expression. The reported data suggest that soft substrates (0.1 to 30 kPa) could play a crucial role both in MSCs differentiation and chondrocytes re-differentiation. However, it is important to note that most studies were performed in the presence of TGF-β thus making it difficult to discern the effect of stiffness alone. For this project hydrogels, cryogels and reinforced melt electrowritten (MEW) cryogels (cryoMEW) of different stiffness have been developed and their role in affecting MSCs differentiation and chondrocytes re- differentiation have been evaluated. By simply increasing the concentration of the crosslinker soft hydrogels of different stiffness were produced. To obtain mechanically stronger hydrogels the preparation method was modified and cryogels were produced, furthermore by incorporating MEW fibres it was possible to enhance the resilience of the cryogels making them suitable for in vivo application. Soft hydrogels supported MSCs differentiation and chondrocytes re-differentiation by allowing cell migration and ECM deposition. Cryogels supported cell viability for both MSCs and chondrocytes as well as increased the expression of several chondrogenic markers. The effect of CryoMEW was studied on dedifferentiated chondrocytes and the results obtained revealed good cell infiltration into the scaffold and the increase of chondrogenic markers. Overall the data presented in this thesis suggested that stiffness plays an important role in affecting cells behaviour and the quality of the ECM produced even without the use of growth factors. Therefore, when developing a scaffold for cartilage repair the mechanical properties should be taken into consideration.
| Date of Award | 20 Feb 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Marta Roldo (Supervisor), Gordon Blunn (Supervisor) & Gianluca Tozzi (Supervisor) |